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Received June 15, 2005
Revised July 12, 2005
Accepted after revision September 8, 2005
1 INSERM U-637; UM1
2 INSERM AVENIR, IFR 52, Collège de France
3 Département de Pharmacologie et de Toxicologie, Université de Lausanne
* To whom correspondence should be addressed. E-mail: benitah{at}montp.inserm.fr.
Aldosterone is involved in a variety of pathophysiological processes that ultimately cause cardiovascular diseases. The physiological role of aldosterone on heart function remains, however, elusive. We took advantage of transgenic mouse models characterized by a renal salt losing (SL) or salt retaining (SR) phenotype, thus exhibiting chronically high or low plasma aldosterone levels, respectively, to investigate the chronic effects of aldosterone in cardiomyocytes devoid of pathology. Upon normal salt diet, these animals indeed do not develop any evidence of cardiovascular disease. Using the whole cell patch-clamp technique on freshly isolated adult ventricular cardiomyocytes, we observed that the amplitude of L-type Ca2+ currents (ICa) correlates with plasma aldosterone levels. Larger ICa are associated with high aldosterone concentrations in SL models, whereas smaller ICa were observed in SR model. Neither the time nor the voltage-dependent properties of ICa varied measurably. In parallel, we determined whether modulation of ICa by blood concentration of aldosterone has a major physiological impact on the excitation-contraction coupling of the cardiomyocytes. Action potential duration, [Ca2+]i transient amplitude and contraction are increased in SL models and vice versa are decreased in SR model. In conclusion, we now show that blood concentration of aldosterone exerts chronic regulation of ICa in mouse cardiomyocytes. This regulation has important consequences on excitation-contraction coupling and, potentially, on other Ca2+-regulated functions in cardiomyocytes.
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